Automatic analyzer

ABSTRACT

A high-throughput automatic analyzer integrates a biochemical analysis section and a blood coagulation analysis section. The analyzer is capable of achieving a reduction in size, system cost, and lifecycle cost. The automatic analyzer includes: a reaction disk; a first reagent dispensing mechanism that dispenses a reagent to reaction cells on the reaction disk; a photometer that irradiates a reaction solution in the reaction cell with light; a reaction cell cleaning mechanism; a reaction vessel supply unit that supplies a disposable reaction vessel for mixing and reacting a sample and a reagent with each other; a second reagent dispensing mechanism that dispenses a reagent to the disposable reaction vessel; a blood coagulation time measuring section that irradiates a reaction solution in the disposable reaction vessel with light to detect transmitted or scattered light; and a sample dispensing mechanism that dispenses a sample to the reaction cell and the disposable reaction vessel.

TECHNICAL FIELD

The present invention relates generally to automatic analyzers thatanalyze amount of components contained in samples such as blood andurine and, more particularly, to an automatic analyzer capable ofmeasuring biochemical analysis items and blood coagulation time items.

BACKGROUND ART

A known automatic analyzer designed to analyze amount of componentscontained in a sample irradiates a reaction solution, in which a sampleand a reagent are mixed with each other, with light from a light source.The analyzer then measures the intensity of the obtained transmitted orscattered light with respect to a single wavelength or a plurality ofwavelengths so as to determine the amount of a component on the basis ofa relation between light intensity and concentration.

The automatic analyzer disclosed in patent document 1 includes areaction disk that repeats rotation and stop, the reaction disk havingoptically transparent reaction cells arranged circumferentially thereon.While the reaction disk is rotating, a transmitted light measuringsection disposed at a predetermined position in the automatic analyzermeasures, for a period of approximately ten minutes, changes in thelight intensity over time as a result of a reaction at predeterminedtime intervals (reaction process data). After the reaction, the reactionvessel is cleaned by a cleaning mechanism before being re-used for otheranalyses.

Two broad types of analysis fields exist for reactions of the reactionsolution: specifically, a colorimetric analysis that uses a colorreaction of a substrate and an enzyme; and a homogeneous immunoassaythat uses an agglutination reaction by bonding of an antigen and anantibody. The immunoturbidimetric method and the latex coagulatingmethod are known for the latter homogeneous immunoassay.

The immunoturbidimetric method uses a reagent containing an antibody toproduce an immune complex with a substance to be measured (an antigen)contained in the sample. The immune complex is then optically detectedto thereby determine component amount. The latex coagulating method usesa reagent that contains latex particles having an antibody sensitized(bonded) to their surfaces. The latex particles are agglutinated throughan antigen-antibody reaction with the antigen contained in the sample.The agglutinated latex particles are then optically detected to therebydetermine component amount. Analyzers performing even higher sensitiveheterogeneous immunoassay are also known. These analyzers employdetection techniques by use of chemoluminescence and electrochemicalluminescence and the B/F separation technique.

Patent document 2 discloses another automatic analyzer that measurescoagulability of blood. Blood has fluidity inside the blood vessel;however, bleeding activates coagulation factors in the blood plasma andplatelet in a chained manner, so that fibrinogen in the blood plasmaturns to form fibrin, causing the bleeding to stop.

Blood coagulability may be exogenous where blood that escapes from theblood vessel coagulates, or endogenous where blood inside the bloodvessel coagulates. Measurement items relating to the blood coagulabilityinclude prothrombin time (PT) as an exogenous blood coagulation reactiontest and activated partial thromboplastin time (APTT) and a fibrinogenamount (Fbg) as an endogenous blood coagulation reaction test.

For each of these measurement items, a reagent that makes coagulationstart is added to thereby cause deposition of fibrin and the resultantfibrin is detected with an optical, physical, or electrical technique. Aknown method employing the optical technique irradiates a reactionsolution with light and identifies fibrin that deposits in the reactionsolution as changes in intensity of scattered light or transmitted lightover time, thereby calculating the time at which the fibrin startsdeposition. In blood coagulation automatic analyzers represented by theautomatic analyzer disclosed in patent document 2, blood coagulationreactions (Fbg item, in particular) feature a short coagulation time, asbrief as several seconds, which requires that the intensity of light bemeasured at short intervals, that is, as short as approximately 0.1seconds. Furthermore, once the reaction solution solidifies, thereaction vessel can no longer be re-used through cleaning. Specifically,the reaction is made at an independent photometric port and the reactionvessel is throwaway. The blood coagulation and fibrinolysis testsinclude measurement of coagulation factors and measurement of thecoagulation-fibrinolysis marker, in addition to measurement of the bloodcoagulation time. The measurement of coagulation factors is taken mainlyat a blood coagulation time measuring section. For thecoagulation-fibrinolysis marker, analyses are made with the syntheticsubstrate method where a chromogenic synthetic substrate is used or thelatex coagulating method mentioned earlier. Whereas the conventionallyavailable PT, APTT, and Fbg are substantially fixed for the bloodcoagulation time items, the number of coagulation-fibrinolysis markeritems are expected to increase to respond to requirements for earlydiagnosis and treatment for disseminated intravascular coagulationsyndromes (DIC), including soluble fibrin monomer complex (SFMC) andplasmin-α2-plasmin inhibitor (PIC), in addition to D dimer and fibrinfibrinogen degradation product (FDP). The need thus exists for improvedthroughput of the automatic analyzers. In the analyzer disclosed inpatent document 2, however, the coagulation-fibrinolysis marker ismeasured at the photometric port at which transmitted light can bemeasured. In conventional blood coagulation analyzers, both thecoagulation time and the coagulation-fibrinolysis marker are generallyanalyzed at a fixed photometric port.

PRIOR ART DOCUMENTS Patent Documents

Patent Document 1: U.S. Pat. No. 4,451,433

Patent Document 2: JP-2000-321286-A

Patent Document 3: JP-2001-013151-A

Patent Document 4: WO2006/107016

Patent Document 5: JP-2011-099681-A

SUMMARY OF THE INVENTION Problem to be Solved by the Invention

Combining a biochemical analyzer with a blood coagulation analyzershould offer advantages of, for example, improved sample managementprocess and greater labor saving in system control. Simply combining thetwo, however, leads to a larger system configuration, higher systemcost, and other problems that are not negligible.

Analysis time generally varies from ten minutes for biochemical items tothree to seven minutes for coagulation time items and thus reducedprocessing capacity may result depending on the analysis time and thetype of detector. Measurement of coagulation time normally takesapproximately three minutes and the processing capacity can bemaintained at a high level by discarding/supplying reaction vessels uponcompletion of the measurement. The synthetic substrate method and thelatex coagulating method are typically a 10-minute reaction, takinglonger time than coagulation time items do. Use of a conventional bloodcoagulation analyzer that includes a fixed port only for measuring theseanalysis items thus results in significantly lower processing capacity.

To solve these problems involved with the combination of analyzers,patent document 3 discloses an automatic analyzer that includes a linearbelt conveyor-driven blood coagulation analysis section and a circularbelt conveyor-driven biochemical analysis section. This configurationrequires that, for an analysis of a biochemical item or a coagulationitem, the reaction vessel be transferred onto the biochemical analysissection by way of the blood coagulation analysis section and thebiochemical analysis section is estimated to have a processing capacityof 200 to 300 [tests/hour]. The capacity falls short of the processingcapacity of the biochemical automatic analyzer disclosed in patentdocument 1 that boasts of 1000 [tests/hour].

The automatic analyzer disclosed in patent document 4 includes a linearbelt conveyor-driven blood coagulation analysis section that can usecommon disposable reaction vessels and a biochemical analysis sectionincluding the disposable reaction vessels. The biochemical analysissection using the disposable reaction vessels is estimated to have aprocessing capacity of 200 to 300 [tests/hour] and it still seemsdifficult to improve the processing capacity by a large margin.

In the blood coagulation time measurement, the reaction starts inseveral seconds after the reagent has been discharged. The automaticanalyzer disclosed in patent document 4 therefore includes a reagentdispensing mechanism having a reagent heating function in order to allowthe temperature of the reaction solution to be kept at 37 degreesCelsius (° C.) immediately following the discharge of the reagent. Ittakes 10 to 20 seconds, however, before the reagent stored in a reagentrefrigerator maintained typically at a temperature of 5° C. to 10° C.can be heated to an adequate temperature. This has been one of thefactors contributing to a decline in processing capacity of the system.

To solve this problem, the technique disclosed in patent document 5preheats the reagent at a turntable-type biochemical analysis section.The technique pertains to effective ways of shortening final reagentheating time by use of the reagent nozzle and stabilizing temperaturecontrol. Simply combining the biochemical analysis section with thecoagulation analysis section does not, however, enables efficient use ofthe reaction cells of the biochemical analysis section, which leads tolower processing capacity of the system.

Since the biochemical analysis sections in patent documents 3 and 4assume use of the disposable reaction vessels, using the disposablereaction vessels only for heating the reagent will increase theconsumable cost. From the viewpoint of lifecycle cost, adoption of thebiochemical analysis sections in patent documents 3 and 4 has beenvirtually impractical.

Means for Solving the Problem

In some aspects, the present invention provides the following.

(1) An automatic analyzer includes: a reaction disk having a reactioncell arranged circumferentially thereon, the reaction cell mixing andreacting a sample and a reagent with each other, the reaction diskrepeating rotation and stop; a first reagent dispensing mechanism thatdispenses a reagent to the reaction cell; a photometer that irradiates areaction solution in the reaction cell with light to thereby detectlight; a reaction cell cleaning mechanism that cleans the reaction cell;a reaction vessel supply unit that supplies a disposable reaction vesselfor mixing and reacting a sample and a reagent with each other; a secondreagent dispensing mechanism with a reagent heating function thatdispenses a reagent to the disposable reaction vessel; a bloodcoagulation time measuring section that irradiates a reaction solutionin the disposable reaction vessel with light to thereby detecttransmitted light or scattered light; and a sample dispensing mechanismthat dispenses a sample to the reaction cell and the disposable reactionvessel.

The automatic analyzer, including the sample dispensing mechanism thatdispenses a sample to the reaction cell and the disposable reactionvessel, can be built more compactly than that including dedicated sampledispensing mechanisms for both the reaction cell and the disposablereaction vessel. In addition, system cost and lifecycle cost can also beprevented from increasing. Moreover, a single system can achieve bothbiochemical analysis and blood coagulation analysis, so that ahigh-throughput automatic analyzer can be provided.

(2) The automatic analyzer of (1) above further includes a controllerthat controls the blood coagulation time measuring section so that onecycle time in an analysis operation cycle of the blood coagulation timemeasuring section is a multiple of n (n being a natural number) of onecycle time in an analysis operation cycle of the reaction disk.

The foregoing arrangement allows a biochemical analyzer to perform bloodcoagulation time measurement without involving a major reduction in itsthroughput even with a blood coagulation time measuring section newlyadded thereto. For example, when n is 2 or more, a timing at which theblood coagulation time measuring section performs an analysis operationfalls on a timing at which a biochemical analysis operation starts atall times, so that there will be no waste of time. Thus, ahigh-throughput automatic analyzer can be provided.

(3) In the automatic analyzer of (1) or (2), control is performed suchthat, at a timing at which a sample is dispensed to the bloodcoagulation time measuring section, the reaction disk is rotated withoutthe sample being dispensed to the reaction cell to thereby produce anempty reaction cell and a reagent for measuring blood coagulation timeis discharged into the empty reaction cell with the use of the firstreagent dispensing mechanism before being preheated.

This allows an empty reaction cell inevitably produced in the bloodcoagulation time measurement to be used for preheating the reagent formeasuring blood coagulation time, enabling an efficient use of thereaction cells. A high-throughput automatic analyzer can thus beprovided.

Advantage of the Invention

An object of the present invention is to provide a high-throughputautomatic analyzer that integrates a biochemical analysis section and ablood coagulation analysis section, and is capable of achieving areduction in size, system cost, and lifecycle cost.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a system block diagram showing a general configuration of aturntable-type automatic analyzer that assumes a base of an embodimentof the present invention.

FIG. 2 is a schematic diagram showing an automatic analyzer including aturntable-type biochemical analysis section and a blood coagulation timemeasuring section according to an embodiment of the present invention.

FIG. 3 is an exemplary diagram showing a blood coagulation timemeasurement sequence for a single-reagent system according to theembodiment of the present invention.

FIG. 4a is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4b is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4c is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4d is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4e is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4f is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4g is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4h is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4i is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 4j is a diagram showing a general mechanical operation in bloodcoagulation time measurement (single-reagent system) according to theembodiment of the present invention.

FIG. 5 is a diagram showing an exemplary pattern of using the reactioncells with respect to an analysis request for biochemical items andblood coagulation time items according to the embodiment of the presentinvention.

FIG. 6 is a schematic diagram showing an automatic analyzer thatincludes a biochemical analysis section, a blood coagulation timemeasuring section, and a heterogeneous immunoassay section according toan embodiment of the present invention.

FIG. 7 is an exemplary diagram showing a blood coagulation timemeasurement sequence for a double-reagent system according to theembodiment of the present invention.

FIG. 8 is a diagram illustrating an embodiment of the present inventionin which a pickup position of a second reagent dispensing mechanism witha reagent heating function is changed in accordance with storage time ofa reagent or a mixture solution.

FIG. 9a is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9b is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9c is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9d is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9e is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9f is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9g is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9h is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9i is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9j is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9k is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 9l is a diagram showing a general mechanical operation in bloodcoagulation time measurement (double-reagent system) according to theembodiment of the present invention.

FIG. 10 is a diagram illustrating a method of estimating coagulationreaction end time according to an embodiment of the present invention.

FIG. 11 is a schematic diagram showing an automatic analyzer thatincludes an amplifier and an amplifier controller according to anembodiment of the present invention.

FIG. 12 is a diagram illustrating a zero level offset function for theamplifier according to the embodiment of the present invention.

MODES FOR CARRYING OUT THE INVENTION

An embodiment of the present invention will be described in detail belowwith reference to the accompanying figures. In all the drawings fordescribing the embodiment, like or corresponding parts are identified bythe same reference numerals and descriptions for those parts will beomitted wherever feasible.

In this description, analysis items for which only a first reagent isused are referred to as a single-reagent system and analysis items forwhich both the first reagent and a second reagent are used are referredto as a double-reagent system.

FIG. 1 is a system block diagram showing a general configuration of aturntable-type automatic analyzer that assumes a base of an embodimentof the present invention. As shown in FIG. 1, this automatic analyzer 1mainly includes a reaction disk 10, a sample disk 20, a first reagentdisk 30 a, a second reagent disk 30 b, a light source 40, a photometer41, and a computer 50.

The reaction disk 10 is capable of intermittent rotation, and aplurality of reaction cells 11 formed of a translucent material ismounted on the reaction disk 10 along a circumferential directionthereof. The reaction cells 11 are maintained at a predeterminedtemperature (for example, at 37° C.) by means of a constant-temperaturebath 12. A temperature of a fluid inside the constant-temperature bath12 is adjusted with a constant-temperature maintaining device 13.

The sample disk 20 has a plurality of sample vessels 21 mounted thereonin two rows extending in the circumferential direction in the exampleshown in FIG. 1, each of the sample vessels 21 containing therein abiological sample such as blood and urine. A sample dispensing mechanism22 is disposed near the sample disk 20. The sample dispensing mechanism22 mainly includes a movable arm 23 and a pipette nozzle 24 attached tothe movable arm 23. The sample dispensing mechanism 22, through theforegoing arrangements, causes the movable arm 23 to move the pipettenozzle 24 to an appropriate dispensing position during a dispensingsequence and causes the pipette nozzle 24 to pick up a predeterminedamount of sample from a sample vessel 21 located at a pickup position inthe sample disk 20 and to discharge the sample into a reaction cell 11at a discharge position on the reaction disk 10.

The first reagent disk 30 a and the second reagent disk 30 b aredisposed inside a first reagent refrigerator 31 a and a second reagentrefrigerator 31 b, respectively. The first reagent refrigerator 31 a andthe second reagent refrigerator 31 b respectively contain a plurality offirst reagent bottles 32 a and a plurality of second reagent bottles 32b respectively placed in a circumferential direction of the firstreagent disk 30 a and the second reagent disk 30 b. The first reagentbottles 32 a and the second reagent bottles 32 b are each affixed with alabel that indicates reagent identification information, such as a barcode. The first reagent bottles 32 a and the second reagent bottles 32 beach store therein a reagent solution that is associated with ananalysis item to be analyzed by the automatic analyzer 1. Additionally,the first reagent refrigerator 31 a and the second reagent refrigerator31 b are provided as an adjunct with a first bar code reader 33 a and asecond bar code reader 33 b, respectively. The first bar code reader 33a and the second bar code reader 33 b read the bar codes indicated onouter walls of the first reagent bottles 32 a and the second reagentbottles 32 b during reagent registration. The read reagent informationis registered in a memory 56, together with a specific position on thefirst reagent disk 30 a or the second reagent disk 30 b.

A first reagent dispensing mechanism 34 a and a third reagent dispensingmechanism 34 b, each having a mechanism substantially identical to thatof the sample dispensing mechanism 22, are disposed near the firstreagent disk 30 a and the second reagent disk 30 b, respectively. Duringthe reagent dispensing, a pipette nozzle included in each of the firstreagent dispensing mechanism 34 a and the third reagent dispensingmechanism 34 b sucks the reagent from the first reagent bottle 32 a orthe second reagent bottle 32 b that is associated with the analysis itemand positioned at a reagent receiving position on the reaction disk 10.The pipette nozzle then discharges the reagent into a correspondingreaction cell 11.

A first agitating mechanism 35 a and a second agitating mechanism 35 bare disposed in an area surrounded by the reaction disk 10, the firstreagent disk 30 a, the second reagent disk 30 b, the first reagentdispensing mechanism 34 a, and the third reagent dispensing mechanism 34b. The first reagent dispensing mechanism 34 a or the third reagentdispensing mechanism 34 b agitates a mixture solution of the sample andthe reagent stored in the reaction cell 11 to thereby promote reaction.

The light source 40 is disposed at a position near a center of thereaction disk 10 and the photometer 41 is disposed on an outerperipheral side of the reaction disk 10. A row of the reaction cells 11that have been subjected to the agitation is rotationally moved so as topass through a photometric position between the light source 40 and thephotometer 41. The light source 40 and the photometer 41 constitute anoptical detection system. The photometer 41 detects transmitted light orscattered light.

A reaction solution of the sample and the reagent in each of thereaction cells 11 are subjected to a photometric process each time thereaction solution passes through the photometer 41 during rotation ofthe reaction disk 10. An analog signal of the scattered light measuredfor each sample is applied to an analog-to-digital (A/D) converter 54.An inside of a used reaction cell 11 is cleaned by a reaction cellcleaning mechanism 36 disposed near the reaction disk 10 to enablerepeated use of the reaction cells 11.

A control system and a signal processing system in the automaticanalyzer 1 will now be described with reference to FIG. 1. The computer50 is connected to a sample dispensing control unit 52, a reagentdispensing control unit 53, and the A/D converter 54 via an interface51. The computer 50 sends a command to the sample dispensing controlunit 52 to thereby control a sample dispensing operation. The computer50 also sends a command to the reagent dispensing control unit 53 tothereby control a reagent dispensing operation. Additionally, thecomputer 50 reads a measured value in the form of a digital signal asconverted by the A/D converter 54.

A printer 55 for printing, the memory 56 and an external output medium57 serving as storages, a keyboard 58 for inputting, for example, anoperational command, and a CRT display (display device) 59 fordisplaying a screen are connected to the interface 51. The displaydevice 59 may be a liquid crystal display, in addition to the CRTdisplay. The memory 56 may include a hard disk memory or an externalmemory. The memory 56 stores therein information such as passwords ofoperators, display levels of different screens, analysis parameters,analysis item requests, calibration results, and analyses.

The following describes how the automatic analyzer 1 shown in FIG. 1analyzes samples. Analysis parameters relating to the items to beanalyzed by the automatic analyzer 1 are previously input via aninformation inputting device, such as the keyboard 58, and stored in thememory 56. The operator selects a test item requested for each sampleusing an operational function screen.

At this time, information such as a patient ID is also input from thekeyboard 58. To analyze the test item specified for each sample, thepipette nozzle 24 of the sample dispensing mechanism 22 dispenses apredetermined amount of the sample from the sample vessel 21 to thereaction cell 11 in accordance with the analysis parameter.

The reaction cell 11 into which the sample has been dispensed istransferred through the rotation of the reaction disk 10 and stops atthe reagent receiving position. The pipette nozzles of the first reagentdispensing mechanism 34 a and the third reagent dispensing mechanism 34b dispense a predetermined amount of the reagent solution to thereaction cell 11 in accordance with the analysis parameter of thecorresponding test item. The order in which the sample and the reagentare dispensed may be opposite to this example; that is, the reagent mayfirst be dispensed before the sample.

The sample and the reagent are thereafter agitated and mixed by thefirst agitating mechanism 35 a and the second agitating mechanism 35 b.When the reaction cell 11 passes through the photometric position, thephotometer 41 measures the transmitted light or the scattered light ofthe reaction solution. The measured transmitted light or scattered lightis translated to a corresponding numerical value that is proportional tolight intensity by means of the A/D converter 54 and the numerical valueis fetched by the computer 50 via the interface 51.

Concentration data is calculated using this converted numerical valueand on the basis of a calibration curve previously measured with ananalysis method specified for each test item. The componentconcentration data as a result of the analysis of each test item isoutput to the printer 55 or a screen of the CRT display 59.

Prior to the performance of the above-described measurement, theoperator sets various parameters and registers the samples, as requiredfor the analysis measurement, via the operational screen of the CRTdisplay 59. In addition, the operator checks analyses obtained after themeasurement using the operational screen on the CRT display 59.

FIG. 2 is a schematic diagram showing an automatic analyzer including aturntable-type biochemical analysis section and a blood coagulation timemeasuring section according to an embodiment of the present invention.The automatic analyzer shown in FIG. 2 includes a sample dispensingmechanism 22 shared between the turntable-type biochemical analysissection and the blood coagulation time measuring section. Compared tothe turntable-type biochemical automatic analyzer shown in FIG. 1, theautomatic analyzer shown in FIG. 2 additionally includes a reactionvessel supply unit 63 keeping a stock of a plurality of disposablereaction vessels 62, a reaction vessel temperature-regulating block 60including a plurality of coagulation time detecting parts 61, a reactionvessel transfer mechanism 65 transferring the disposable reactionvessels 62, a second reagent dispensing mechanism with a reagent heatingfunction 66, a coagulation time sample dispensing position 64, and areaction vessel discard section 67.

FIG. 3 is an exemplary diagram showing a blood coagulation timemeasurement sequence for the single-reagent system according to theembodiment of the present invention. The sample discharged to thedisposable reaction vessel 62 is heated by the coagulation timedetecting parts 61 included in the reaction vesseltemperature-regulating block 60 of a blood coagulation analysis section(b to d) and the reagent is preheated (to 37° C.) at the reaction cell11 on the reaction disk 10 of the biochemical analysis section (i to j).The reagent preheated to 37° C. is further heated by the second reagentdispensing mechanism with a reagent heating function 66 (to, forexample, 40° C.) and discharged into the disposable reaction vessel 62that contains therein the sample heated to 37° C. in advance, whereby ablood coagulation reaction is started (e). After the reaction (f),coagulation time is calculated (g) and the disposable reaction vessel 62is discarded at the reaction vessel discard section 67 (h). The firstreagent dispensing mechanism 34 a or the third reagent dispensingmechanism 34 b discharges cleaning water or a cleaning agent into thereaction cell 11 from which the preheated reagent has been sucked (k).And the reaction cell 11 is thereafter cleaned by the reaction cellcleaning mechanism 36 (l).

A general mechanical operation in blood coagulation time measurement(the single-reagent system) will now be described with reference toFIGS. 4a to 4j . FIG. 4a shows that the reaction vessel transfermechanism 65 has already moved the disposable reaction vessel 62 fromthe reaction vessel supply unit 63 to the coagulation time sampledispensing position 64, from which status the blood coagulation timemeasurement is started. The sample sucked by the sample dispensingmechanism 22 passes through the sample dispensing position in thebiochemical analysis section and is dispensed to the disposable reactionvessel 62 at the coagulation time sample dispensing position 64 (FIGS.4a and 4b ). At this time, an empty reaction cell 11 not to be used forthe analysis is produced at the reaction disk 10 (FIG. 4b ). Thedisposable reaction vessel 62 to which the sample has been dispensed istransferred by the reaction vessel transfer mechanism 65 onto thecoagulation time detecting part 61 included in the reaction vesseltemperature-regulating block 60 and the sample is heated to 37° C.(FIGS. 4c and 4d ). Meanwhile, the first reagent dispensing mechanism 34a dispenses the reagent for measuring blood coagulation time to theempty reaction cell 11 which is then preheated to 37° C. over aplurality of cycles (FIGS. 4c and 4d ). The number of cycles for thepreheating is set in advance in accordance with the time required by thereaction vessel temperature-regulating block 60 to heat the sample. Thereagent that has been completely preheated is positioned at a bloodcoagulation reagent pickup position and sucked by the second reagentdispensing mechanism with a reagent heating function 66 (FIGS. 4e and 4f). The reagent for measuring blood coagulation time is first heated bythe second reagent dispensing mechanism with a reagent heating function66 to a predetermined required temperature (e.g., 40° C.) so as to havea temperature of 37° C. immediately after the discharge. The reagent isthereafter discharged into the disposable reaction vessel 62 thatcontains therein the sample (FIG. 4g ). At this time, a spurt of thereagent being discharged agitates the sample and the reagent and asequence to measure the blood coagulation time starts (FIG. 4h ). Thedisposable reaction vessel 62 that has been subjected to the bloodcoagulation time measurement is discarded to the reaction vessel discardsection 67 by the reaction vessel transfer mechanism 65 (FIGS. 4i and 4j).

As described above, the reaction disk is rotated without the samplebeing dispensed thereto to thereby produce an empty reaction cell at atiming at which the sample is dispensed to the blood coagulation timemeasuring section. The first reagent dispensing mechanism 34 a is thenemployed to discharge the reagent for measuring blood coagulation timeinto the empty reaction cell and the reagent for measuring bloodcoagulation time is preheated. This control procedure enables use of theempty reaction cell inevitably produced in the blood coagulation timemeasurement for preheating the reagent for measuring blood coagulationtime, thus achieving an efficient use of the reaction cells. Anautomatic analyzer offering a high throughput can thus be provided. Itis also known that the reagent is mounted on the reagent disk and istransferred from the reagent disk to the blood coagulation timemeasuring section by way of the reaction disk. In setting the system,the foregoing configuration eliminates the need for a new coldinsulation container for the reagent for measuring blood coagulationtime and for a reagent dispensing mechanism requiring a long distancetravel, so that an increase in system cost can be minimized.

The first reagent dispensing mechanism 34 a or the third reagentdispensing mechanism 34 b discharges, after several cycles, cleaningwater or the cleaning agent into the reaction cell 11 from which thepreheated reagent for measuring blood coagulation time has been sucked.The reaction cell 11 is cleaned, after another several cycles, by thereaction cell cleaning mechanism 36 (FIG. 4g ).

Preferably, the first reagent dispensing mechanism 34 a that dispensesthe reagent for measuring blood coagulation time is a reagent dispensingmechanism that dispenses the first reagent in the biochemical analysissection. The first reagent is discharged into the reaction vessel at acycle close to a timing at which the sample is dispensed. The firstreagent dispensing mechanism 34 a is disposed so as to achieve theforegoing purpose. Thus, there is no need to change the conventionalturntable-type driving method when dispensing the reagent for measuringblood coagulation time. In addition, the reagent dispensing mechanismcan be shared between the biochemical analysis section and the bloodcoagulation time measuring section, so that further reduction in sizecan be achieved.

The third reagent dispensing mechanism 34 b that dispenses the cleaningwater or the cleaning agent into the reaction cell 11 from which thereagent for measuring blood coagulation time has been sucked may beidentical to the first reagent dispensing mechanism 34 a. In thebiochemical analysis section, however, the third reagent dispensingmechanism 34 b preferably dispenses the second reagent. The secondreagent is discharged after the first reagent has been discharged intothe reaction cell. And the third reagent dispensing mechanism 34 b isdisposed so as to achieve this operation. This disposition eliminatesthe need for changing the conventional turntable-type driving method inorder to clean the reaction cell that stores therein the reagent formeasuring blood coagulation time. Additionally, the reagent dispensingmechanism can be shared between the biochemical analysis section and theblood coagulation time measuring section, so that further reduction insize can be achieved.

The reaction disk repeats a cycle of rotating a predetermined rotationalangle and stopping. It is therefore preferable that the second reagentdispensing mechanism 66 be disposed in consideration of its dispensingposition such that a specific reaction cell visits in sequence adispensing position of the first reagent dispensing mechanism 34 a, thatof the second reagent dispensing mechanism 66, and that of the thirdreagent dispensing mechanism 34 b. This is because of the followingreason: specifically, the cleaning by the reaction cell cleaningmechanism 36 can be achieved at an identical number of cycles withreference to the dispensing of the reagent for measuring bloodcoagulation time and the dispensing of the first reagent, so that ahigher throughput can be promoted.

FIG. 5 shows an exemplary pattern of using the reaction cells 11 on thereaction disk 10 with respect to an analysis request for biochemicalitems and blood coagulation time items according to the embodiment ofthe present invention. In FIG. 5, one cycle time in an analysisoperation cycle of the blood coagulation time measuring section is twiceas long as one cycle time in an analysis operation cycle of thebiochemical analysis section. As described with reference to FIGS. 4a to4j , the blood coagulation time measuring section is required to performsuch an operation as the transfer of the disposable reaction vesselwithin the one-cycle time. Thus, the one-cycle time in the analysisoperation of the blood coagulation time measuring section may preferablybe longer than the one-cycle time in the analysis operation of thebiochemical analysis section. The fact is, however, not as simple as theidea that the one-cycle time only has to be longer. Specifically, theone cycle time in the analysis operation of the blood coagulation timemeasuring section is longer by a multiple of a natural number than theone-cycle time in the analysis operation of the biochemical analysissection so that a timing at which the blood coagulation time measuringsection performs the analysis operation coincides with a timing at whichthe biochemical analysis section starts to perform the analysisoperation at all times.

Assume that measurement requests are made as shown in the upper diagramin FIG. 5 with respect to the coagulation time items for thesingle-reagent system. The upper diagram in FIG. 5 shows thatmeasurement requests for coagulation 1 and coagulation 2 occurconsecutively. Because the one-cycle time in the analysis operation ofthe blood coagulation time measuring section is double the one-cycletime in the analysis operation of the biochemical analysis section asdescribed above, the use of the reaction cells in the order of themeasurement requests will disable processing performed by the bloodcoagulation time measuring section that requires twice as long one cycletime as that of the biochemical analysis section. Take, for instance, 4seconds and 8 seconds. Whereas the reaction disk makes one rotation andone stop in 4 seconds, the reaction vessel supply unit 63 that keeps astock of a plurality of disposable reaction vessels 62 to be used formeasurement, the reaction vessel transfer mechanism 65 that transfersthe disposable reaction vessels 62, and the second reagent dispensingmechanism with a reagent heating function 66 are controlled to be drivenat a cycle of 8 seconds. In the example shown in the upper diagram ofFIG. 5, therefore, the order of the reaction cells to be used iscontrolled to be changed so that the blood coagulation time measurementfor coagulation 1 can be performed at a cycle of 8 seconds by insertingbiochemical 1 between coagulation 1 and coagulation 2. As is known fromthe above, the reaction cells 11 are to be alternately used for reagentpreheating even when coagulation time items are consecutively requested.Suppose that the one-cycle time in the analysis operation cycle of theblood coagulation time measuring section is n-fold and coagulation timeitems are consecutively requested. Control is then performed to changethe order of the reaction cells to be used such that n−1 biochemicalanalysis items are inserted.

Assume that measurement requests are made as shown in the lower diagramin FIG. 5 with respect to the coagulation time items for thedouble-reagent system. The measurement requests include coagulation 1 ofthe double-reagent system. While the need is to independently preheattwo reagents of coagulation 1 a and coagulation 1 b and move the tworeagents to the disposable reaction vessel, because of the twice as longone-cycle time involved, the blood coagulation time measuring section isunable to perform processing if reaction cells are used consecutivelyfor coagulation 1 a and coagulation 1 b. Control is therefore performedsuch that, in addition to one extra empty reaction cell being providedper sample for these two reagents, one extra empty reaction cell isprovided and the order of reaction cells is changed so that, instead ofproviding empty reaction vessels consecutively, biochemical 1immediately following coagulation 1 is moved up and coagulation 1 a andcoagulation 1 b alternate with each other. Specifically, although atiming has arrived at which biochemical 2 is dispensable, one cycle iswaited for the reaction cell for coagulation 1 b without dispensing thesample for biochemical 2 therein. This control enables efficientprocessing even when reagents in the single-reagent system and in thedouble-reagent system are mixed with other. With the n-fold one-cycletime, control is performed to change the order of the reaction cells tobe used such that n−1 biochemical analysis items are inserted betweencoagulation 1 a and coagulation 1 b.

Even with a mixture of events of the upper and lower diagrams, controlis performed to change the order of the reaction cells to be used forthe n-fold one-cycle time such that n−1 biochemical analysis items areinserted between reaction cells containing a coagulation reagent.Understandably, however, n−1 cycles are to be waited for the absence ofa request for biochemical analysis measurement. The control performed inFIG. 5 is performed by, for example, a controller included in thecomputer 50 shown in FIG. 1.

FIG. 6 is a schematic diagram showing an automatic analyzer thatincludes a biochemical analysis section, a blood coagulation timemeasuring section, and a heterogeneous immunoassay section according toan embodiment of the present invention. A detecting section ofheterogeneous immunoassay 68 for heterogeneous immunoassay itemmeasurement and a B/F separating mechanism 69 are disposed in anoperable range of the reaction vessel transfer mechanism 65. Thedisposable reaction vessels 62, the reaction vesseltemperature-regulating block 60, the reaction vessel transfer mechanism65, the reaction vessel supply unit 63, and the reaction vessel discardsection 67 are shared with the blood coagulation time measuring section.An automatic analyzer offering an even greater number of enhancedfunctions can thus be configured through the addition of minimumessential mechanisms. It is to be noted that, in FIG. 6, a disk ofreagent of heterogeneous immunoassay 70 is added in an operable range ofthe second reagent dispensing mechanism with a reagent heating function66. The configuration of this embodiment can provide a high-throughputautomatic analyzer with a short TAT that integrates a biochemicalanalysis section, a blood coagulation analysis section, and an analysissection of heterogeneous immunoassay, while achieving a reduction insize, system cost, and lifecycle cost.

The operation described with reference to FIG. 5 was that, for theanalysis items of both the single-reagent system and the double-reagentsystem, the sample dispensing mechanism is used to dispense the samplein the disposable reaction vessel before either the first reagent or thefirst reagent and the second reagent are preheated in the reaction cell.The following describes another example in which the sample for theanalysis items of the single-reagent system is dispensed to thedisposable reaction vessel with the use of the sample dispensingmechanism, and the sample for the analysis items of the double-reagentsystem is dispensed to the reaction cell with the use of the sampledispensing mechanism. An exemplary analysis item of the single-reagentsystem includes prothrombin time (PT) and an exemplary analysis item ofthe double-reagent system includes activated partial thromboplastin time(APTT). For a fibrinogen amount (Fbg), the first reagent being a dilutedsolution is, however, treated as the double-reagent system. While FIGS.3, 4 a to 4 i, and the upper diagram of FIG. 5 show the measurementsequence for the single-reagent system, FIGS. 7 to 9 l show themeasurement sequence for the double-reagent system.

FIG. 7 is an exemplary diagram showing a blood coagulation timemeasurement sequence for the double-reagent system according to theembodiment of the present invention. In this example, the sampledispensing control unit 52 controls the sample dispensing mechanism inaccordance with the analysis item measured at the blood coagulation timemeasuring section: specifically, the sample dispensing mechanism iscontrolled so as to dispense the sample to the disposable reactionvessel when the analysis item is associated with the single-reagentsystem and to dispense the sample to the reaction cell when the analysisitem is associated with the double-reagent system.

After the sample is dispensed to a reaction cell 11, the first reagentdispensing mechanism 34 a discharges a first reagent or a dilutedsolution to the reaction cell 11, so that preheating is started of amixture solution of either the sample and the first reagent or thesample and the diluted solution (h to i). Moreover, after apredetermined number of cycles, the first reagent dispensing mechanism34 a discharges a second reagent to a second reaction cell 11 andpreheating is started (j).

A disposable reaction vessel 62 is moved to a coagulation time detectingpart 61 included in the reaction vessel temperature-regulating block 60of the blood coagulation analysis section (b). The mixture solution andthe second reagent preheated to 37° C. in the reaction cell 11 on thereaction disk 10 of the biochemical analysis section are each sucked bythe second reagent dispensing mechanism with reagent heating function 66(k to l) and are further heated (to, for example, 40° C.) before beingdischarged to the disposable reaction vessel 62 (c to d). Theseoperations will make a blood coagulation reaction start. After thereaction is completed (e), the coagulation time is calculated (f) andthe disposable reaction vessel 62 is discarded in the reaction vesseldiscard section 67 (g).

Thus, in the blood coagulation time measurement sequence for thedouble-reagent system shown in FIG. 7, the sample dispensing mechanism22 dispenses the sample to the reaction cell and the first reagentdispensing mechanism 34 a dispenses the first reagent or the dilutedsolution to the reaction cell; after the resultant mixture solution isstored in the reaction cell for a predetermined period of time, thesecond reagent dispensing mechanism with reagent heating function 66dispenses the mixture solution in the disposable reaction vessel. Thesecond reaction cell that contains therein the reagent (the secondreagent) for starting the blood coagulation reaction to be dischargedinto the disposable reaction cell is provided separately from thereaction cell that contains therein the mixture solution. The sampledispensing control unit 52 controls the sample dispensing mechanism sothat the reaction disk is rotated without the sample being dispensed tothe second reaction cell to thereby make the second reaction cell anempty reaction cell. This control results in the reagent (the secondreagent) for starting the blood coagulation reaction being dischargedinto the empty second reaction cell. The discharge allows the mixturesolution, in addition to the second reagent, to be preheated.

The first reagent dispensing mechanism 34 a or the third reagentdispensing mechanism 34 b discharges the cleaning water or the cleaningagent into the reaction cell 11 from which the preheated mixturesolution or second reagent has been sucked (m to n). The reaction cell11 is thereafter cleaned by the reaction cell cleaning mechanism 36 (o).

The timing at which to dispense the second reagent can be set to anyvalue with resolution of the operating cycle for each analysis item.This allows storage time to be efficiently allotted without changing theconventional driving method of the turntable type in such items as APTTrequiring time for activation or pre-treatment by use of the firstreagent. Specifically, it is preferable the time be varied in accordancewith the analysis item by changing a timing at which to provide an emptycell for storing the second reagent on the basis of the analysis item,the time being required for the reagent (the second reagent) forstarting the blood coagulation reaction to be discharged into themixture solution after the mixture solution has been mixed. To keep thesystem control simple, it is preferable a period of time be set thatbegins when the first reagent dispensing mechanism discharges the secondreagent and ends when the second reagent dispensing mechanism dischargesthe second reagent. In such a case, a timing at which to provide anempty cell for the second reagent after the sample has been dischargedinto the reaction cell may be determined uniformly regardless of theanalysis item. Meanwhile, some analysis items have ideal time to add thesecond reagent after the sample and the first reagent have been mixedwith each other. Thus, preferably, the time to add the second reagent isadjusted in accordance with the analysis item by varying the timing atwhich to provide the empty cell for storing the second reagent afterdispensing of the sample in accordance with the analysis item.

FIG. 8 shows a modification of the second reagent dispensing mechanism.The second reagent dispensing mechanism described above sucks a liquidfrom a single place on the reaction disk. FIG. 8 illustrates anexemplary second reagent dispensing mechanism capable of dispensing aliquid from reaction cells disposed at different positions on thereaction disk. As shown in FIG. 8, the second reagent dispensingmechanism with a reagent heating function 66 is capable of beingpositioned at a plurality positions (1) to (3) on the reaction disk 10to thereby possibly allot time for activation or pre-treatment by use ofthe first reagent based on the pickup position. Additionally, theforegoing method may even be employed for controlling the storage timedepending on the amount of mixture solution or reagent to make up forthe time required for the preheating becoming longer with the increasein the amount of liquid to be preheated. It is therefore preferable thatthe dispensing position be varied in accordance with the type of liquidor the amount to be dispensed by making the second reagent dispensingmechanism capable of dispensing from reaction cells disposed atdifferent positions. While the example shown in FIG. 8 illustrates thatthe second reagent dispensing mechanism is capable of dispensing aliquid from three positions, the number of positions from which todispense a liquid may be two, four or more.

The following describes with reference to FIGS. 9a to 9l a generalmechanical operation in blood coagulation time measurement in thedouble-reagent system in an embodiment of the present invention. FIG. 9a, though indicating that all coagulation time detecting parts 61 are inmeasurement cycles, shows a condition in which measurement end time isfixed at one of the coagulation time detecting parts 61. When theanalysis item is associated with the double-reagent system, the sampledispensing mechanism 22 sucks a sample at this time and dispenses thesample in a reaction cell 11 (FIG. 9b ). The starting of sampledispensing for the double-reagent system upon the fixing of themeasurement end time as described above shortens wait time to enable anefficient analysis, so that an automatic analyzer with a high throughputcan be provided. A predetermined period of time is required before thesample is dispensed to the disposable reaction vessel after the samplehas been dispensed to the reaction cell. This allows the sample to bedispensed to the reaction cell even when all coagulation time detectingparts 61 are occupied. Alternatively, as a method of shortening the waittime, it is also effective to start the sample dispensing for thedouble-reagent system on the basis of the maximum measurement time. Forexample, with the maximum measurement time set to 300 seconds, thedisposable reaction vessel with which the measurement time elapses 300seconds is set to be discarded regardless of whether the measurement endtime is fixed. Assume that it takes 60 seconds to discharge the mixturesolution to the disposable reaction vessel after the sample has beendischarged to the reaction cell [(h) to (k) and (c) in FIG. 7]. It isthen effective as a method of shortening the wait time to perform thesample dispensing with reference to 240 seconds that are obtained bysubtracting 60 seconds from 300 seconds.

One possible method of fixing the measurement end time is to estimatereaction end time on the basis of a peak of results of differentiationof the reaction process. FIG. 10 illustrates this method. In FIG. 10,the abscissa represents time and the ordinate represents lightintensity. FIG. 10 shows reaction process data curves (solid lines) ofmeasurements obtained from the coagulation time detecting parts andfurther shows results of differentiation of the reaction curves (brokenlines). The upper diagram of FIG. 10 shows results of firstdifferentiation, while the lower diagram of FIG. 10 shows results ofsecond differentiation. Approximate reaction end time can be estimatedfrom the peak of the results of either differentiation. Thus, thereaction end time is estimated on the basis of the peak time of theresults of differentiation to thereby determine the reaction end timebefore the estimated time elapses. This enables the use of the peak timeof the results of differentiation as reference for the start of sampledispensing.

As described above, preferably, the blood coagulation time measuringsection includes a plurality of coagulation time detecting parts 61 onwhich the disposable reaction vessels are placed; if all coagulationtime detecting parts 61 are occupied by the disposable reaction vessels,the blood coagulation time measuring section schedules items fordispensing samples in the reaction cells on the basis of a point in timeat which the measurement end time is fixed with reference to apredetermined reaction end criterion or predetermined maximummeasurement time; the blood coagulation time measuring section therebydispenses a sample associated with the scheduled item to the reactioncell with all the coagulation time detecting parts 61 occupied. Thereaction end criterion can be established on the basis of the peak timeof the results of differentiation of the reaction process data curve asthe measurements obtained from the coagulation time detecting parts.

Reference is made back to FIGS. 9a to 9l for the general operation. Thefirst reagent dispensing mechanism 34 a discharges the first reagent orthe diluted solution into the reaction cell 11 in which the sample hasbeen dispensed (FIG. 9c ). The sample and the first reagent or thediluted solution may be agitated by means of a spurt of the reagentbeing discharged or the first agitating mechanism 35 a not shown. Theagitation by the first agitating mechanism 35 a is likely to promote andstabilize the reaction. The mixture solution of the sample and the firstreagent or the diluted solution is preheated to 37° C. on the reactiondisk 10. During this time, a reference value relating to an amount of aninterfering substance in the sample can be calculated throughmeasurement of transmitted light or scattered light taken by thephotometer 41. Specifically, the reference value relating to the amountof the interfering substance contained in the sample can be calculatedwhile the mixture solution is stored in the reaction cell.

To measure absorbance of the mixture solution of the sample and thefirst reagent or the diluted solution using the photometer 41, degreesof turbidity, hemolysis, and yellow color are calculated with absorbancevalues of 480 nm, 505 nm, 570 nm, 600 nm, 660 nm, and 700 nm on thebasis of the following expressions.Turbidity (L)=(1/C)×(difference in absorbance between 660 nm and 700 nm)Hemolysis (H)=(1/A)×(difference in absorbance between 570 nm and 600nm−B×difference in absorbance between 660 nm and 700 nm)Yellowness (I)=(1/D)×(difference in absorbance between 480 nm and 505nm−E×difference in absorbance between 570 nm and 600 nm)−F×difference inabsorbance between 660 nm and 700 nm)

where C, A, and D are: Coefficients for outputting absorbance as seruminformation

B, E, and F are: Coefficients for correcting an overlap of absorptionspectrum

Furthermore, measurements taken with the disposable reaction vessel canbe corrected on the basis of the reference value relating to the amountof the interfering substance. For example, a correlation between thisreference value and the light intensity in coagulation time measurementmay be obtained to thereby correct the coagulation time measurements.

Offset control of an amplifier may be performed with the use of thisreference value. FIG. 11 shows this amplifier and an amplifiercontroller. The coagulation time detecting parts 61 include a detector,an amplifier 71, and an amplifier controller 72. The detector detectsthe transmitted light or the scattered light detected through thedisposable reaction vessel. The amplifier 71 amplifies signals from thedetector. The amplifier controller 72 controls the amplifier 71. Theamplifier controller 72 acquires a reference value relating to theamount of interfering substance and, on the basis of the referencevalue, is capable of offsetting a zero level of the amplifier before thedetector detects the light. FIG. 12 shows measurements of the photometer41 (upper diagram) and measurements of the coagulation time detectingparts 61 (lower diagram). For example, the amplifier controller 72 maybe controlled so that the zero level of the amplifier 71 that amplifiessignals of the coagulation time detecting parts 61 is offset on thebasis of a difference between the measurements of the transmitted lightor the scattered light taken by the photometer 41 (the reference valuerelating to the amount of the interfering substance) and thepredetermined reference level. This control makes it possible to achievemeasurements with an appropriate amplification factor without involvinginability of measurement due to an over-range measurement (FIGS. 11 and12). This reduces frequency of events where the measurements beingunable to be performed and achieves analyses with a minimum of waste ofsamples and reagents.

The correction and the zero level offset described above are alsoapplicable to other analysis items that employ the same sample, becauseone measurement of the reference value can be used for other analysisitems as long as the sample remains the same. The photometer 41 on thereaction disk side is not involved particularly in the analysis itemassociated with the single-reagent system, so that this photometer 41cannot be used to directly measure the amount of the interferingsubstance. Preferably, therefore, corrections are made of measurementdata taken from, among the samples used for other analysis items usingthe same sample, the sample with respect to the analysis itemsassociated with the single-reagent system and the zero level is offsetprior to the measurement.

Reference is made back to FIGS. 9a to 9l for the general operation. Thereaction vessel transfer mechanism 65 discards the disposable reactionvessel 62 that has been subjected to the measurement in the reactionvessel discard section 67 (FIGS. 9d and 9e ). The first reagentdispensing mechanism 34 a discharges the second reagent at apredetermined timing into another reaction cell 11 different from thereaction cell 11 containing therein the mixture solution, the anotherreaction cell 11 being preheated to 37° C. on the reaction disk 10 (FIG.9d ). The reaction vessel transfer mechanism 65 holds a disposablereaction vessel 62 on the reaction vessel supply unit 63 (FIG. 9f ) andmoves the disposable reaction vessel 62 onto the coagulation timedetecting parts 61 (FIG. 9g ). The mixture solution that has beenpreheated is positioned at the blood coagulation reagent pickup positionand sucked by the second reagent dispensing mechanism with a reagentheating function 66 (FIGS. 9g and 9h ). The mixture solution, firstheated by the second reagent dispensing mechanism with a reagent heatingfunction 66 to a preset required temperature (e.g., 40° C.) so as tohave a temperature of 37° C. at a timing immediately after it isdischarged, is then discharged into the disposable reaction vessel 62(FIG. 9i ). The second reagent that has been preheated is thereafterpositioned at the blood coagulation reagent pickup position and suckedby the second reagent dispensing mechanism with a reagent heatingfunction 66 (FIGS. 9j and 9k ). As with the mixture solution, the secondreagent is first heated by the second reagent dispensing mechanism witha reagent heating function 66 to a preset required temperature (e.g.,40° C.) so as to have a temperature of 37° C. at a timing immediatelyafter it is discharged and is then discharged into the disposablereaction vessel 62 (FIG. 9l ). At this time, the mixture solution andthe second reagent are agitated by means of a spurt of the secondreagent being discharged and measurement of the blood coagulation timeis started. The disposable reaction vessel 62 that has been subjected tothe measurement is discarded by the reaction vessel transfer mechanism65 into the reaction vessel discard section 67.

In coagulation time items exemplified by the thrombin reagent of the Fbgitem, it is known that carry-over can affect subsequent measurements ofcoagulation time. Mounting a plurality of reagent dispensing mechanismsmay be one of the solutions to the reagent carry-over problem; however,this involves complicated mechanisms with a resultant increase in systemcost. The first reagent dispensing mechanism 34 a and the second reagentdispensing mechanism with a reagent heating function 66 can be cleanedefficiently by the following procedure: specifically, the first reagentdispensing mechanism 34 a sucks and discharges the cleaning agent intothe reaction cell 11 in a cycle following the discharge of the reagentin the reaction cell 11, and the second reagent dispensing mechanismwith a reagent heating function 66 sucks and discharges the cleaningagent in the reaction cell 11 in a cycle following the pickup anddischarge of the preheated reagent. In addition, the cleaning agent usedfor the first reagent dispensing mechanism 34 a is also used forcleaning the second reagent dispensing mechanism with a reagent heatingfunction 66. This reduces consumption of the cleaning agent.Specifically, it is preferable in terms of reduction in the consumptionof the cleaning agent that, depending on the item, the first reagentdispensing mechanism, after having discharged the reagent, pick up thecleaning agent and then discharge the previously-sucked cleaning agentinto the reaction cell, and that the second reagent dispensing mechanismpick up the cleaning agent from the reaction cell into which thecleaning agent has been discharged and discharge the cleaning agentsucked earlier into a cleaning bath (not shown).

REFERENCE NUMERALS

-   1 automatic analyzer-   10 reaction disk-   11 reaction cell-   12 constant-temperature bath-   13 constant-temperature maintaining device-   20 sample disk-   21 sample vessel-   22 sample dispensing mechanism-   23 movable arm-   24 pipette nozzle-   30 a first reagent disk-   30 b second reagent disk-   31 a first reagent refrigerator-   31 b second reagent refrigerator-   32 a first reagent bottles-   32 b second reagent bottles-   33 a first bar code reader-   33 b second bar code reader-   34 a first reagent dispensing mechanism-   34 b third reagent dispensing mechanism-   35 a first agitating mechanism-   35 b second agitating mechanism-   36 reaction cell cleaning mechanism-   40 light source-   41 photometer-   50 computer-   51 interface-   52 sample dispensing control unit-   53 reagent dispensing control unit-   54 A/D converter-   55 printer-   56 memory-   57 external output medium-   58 keyboard-   59 CRT display (display device)-   60 reaction vessel temperature-regulating block-   61 coagulation time detecting part-   62 disposable reaction vessel-   63 reaction vessel supply unit-   64 coagulation time sample dispensing position-   65 reaction vessel transfer mechanism-   66 second reagent dispensing mechanism with a reagent heating    function-   67 reaction vessel discard section-   68 detecting section of heterogeneous immunoassay-   69 B/F separating mechanism-   70 disk of reagent of heterogeneous immunoassay-   71 amplifier-   72 amplifier controller

The invention claimed is:
 1. An automatic analyzer system comprising abiochemical analysis section and a blood coagulation time measuringsection, wherein the biochemical analysis section includes: a rotatablereaction disk having a plurality of reaction cells disposed at acircumference thereof; a sample dispensing mechanism configured todispense one or more samples, disposed adjacent to the reaction disk andadjacent to a disposable reaction vessel located at a dispensingposition outside of the reaction disk, wherein the sample dispensingmechanism is shared between the biochemical analysis section and theblood coagulation time measuring section; a first reagent dispensingmechanism configured to dispense one or more reagents disposed adjacentto the reaction disk; a light source configured to irradiate a reactionsolution including one of the samples and one of the reagents in one ofthe reaction cells of the reaction disk with light; a photometerconfigured to detect transmitted light or scattered light from theirradiated reaction solution in the one of the reaction cells; areaction cell cleaning mechanism configured to clean the reactionsolution from the one of the reaction cells; wherein the bloodcoagulation time measuring section includes: a detector for measuringblood coagulation time; a temperature regulating block which has one ormore blood coagulation time detectors disposed adjacent to thedispensing position; a reaction vessel transfer mechanism configured tomove the disposable reaction vessel from the dispensing position to oneof the blood coagulation time detectors; a second reagent dispensingmechanism with a reagent heating function disposed adjacent to thereaction disk; the automatic analyzer system further comprising acontroller that is connected to the rotatable reaction disk, the sampledispensing mechanism, the first reagent dispensing mechanism, the lightsource, the photometer, the reaction cell cleaning mechanism, and theblood coagulation time measuring section, wherein the controller isconfigured to control the reaction disk to rotate, the sample dispensingmechanism to dispense one or more of the samples to the reaction cellslocated on the reaction disk and dispense one of the samples to thedisposable reaction vessel located at the dispensing position, and thefirst reagent dispensing mechanism to dispense one or more reagents tothe reaction cells, wherein the controller is further configured tocontrol the reaction disk to rotate and the light source to irradiate areaction solution in one of the reaction cells with light, and thephotometer to detect the transmitted light or the scattered light fromthe irradiated reaction solution in the one of the reaction cells, andthe reaction cell cleaning mechanism to clean the reaction solution fromthe one of the reaction cells after detection by the photometer, whereinthe controller is further configured to control the reaction vesseltransfer mechanism to move the disposable reaction vessel from thedispensing position to one of the blood coagulation time detectors afterthe sample dispensing mechanism has dispensed the one of the samples tothe disposable reaction vessel located at the dispensing position, theone of the blood coagulation time detectors to heat the one of thesamples in the disposable reaction vessel, the second reagent dispensingmechanism to suction one of the reagents from one of the reaction cells,the one of the reagents being a coagulation reagent for measuring bloodcoagulation time, heat the suctioned coagulation reagent, and dispensethe heated coagulation reagent to the disposable reaction vesseldisposed at the one of the blood coagulation time detectors to start ablood coagulation reaction of the one of the samples and the coagulationreagent in the disposable reaction vessel disposed at the one of theblood coagulation time detectors, wherein when an analysis item measuredby the blood coagulation time measuring section is an analysis item of asingle-reagent system the controller is configured to control the sampledispensing mechanism such that a sample is dispensed into a disposablereaction vessel arranged at the dispensing position, and when the sampleis an analysis item of a double reagent system, the sample dispensingmechanism is controlled so as to dispense a sample into a reaction cellheld in the reaction disk, wherein one cycle time of an analysisoperation cycle of the blood coagulation time measuring section is amultiple of n (n being a natural number) of a one cycle time of ananalysis operation cycle of the biochemical analysis section, whereinwhen there is an analysis request of a biochemical item and a bloodcoagulation time analysis item and the blood coagulation time analysisitem is associated with a single-reagent system, the controllerdetermines the order of use of the reaction cells is determined suchthat (n−1) number of reaction cells are used for biochemical analysisamong n reaction cells corresponding to one cycle time of the analysisoperation of the blood coagulation time measuring section, and whereinwhen there is an analysis request of a biochemical item and a bloodcoagulation time analysis item and the blood coagulation time analysisitem is associated with a double-reagent system the controllerdetermines the order of use of the reaction cells such that (n−1) numberof reaction cells are used for biochemical analysis, among n reactioncells corresponding to one cycle time of an analysis operation cycle foreach of the single-reagent and/or double-reagent for measuring bloodcoagulation time.
 2. The automatic analyzer according to claim 1,wherein the controller is further configured to control, when theanalysis item is associated with the double-reagent blood coagulationreaction, the sample dispensing mechanism to dispense the one of thesamples to the one of the reaction cells and the first reagentdispensing mechanism to dispense one of the reagents to the one of thereaction cells.
 3. The automatic analyzer according to claim 1, whereinthe controller is further configured to control, when the analysis itemis associated with the double-reagent blood coagulation reaction andwhen the reaction solution including the one of the samples and the oneof the reagents has been stored in the one of the reaction cells for apredetermined period of time, the sample dispensing mechanism to suctionthe reaction solution and dispense the reaction solution to thedisposable reaction vessel at the dispensing position, and, when thereaction vessel transfer mechanism has moved the disposable reactionvessel from the dispensing position to one of the blood coagulation timedetectors, the second reagent dispensing mechanism to dispense theheated one of the reagents to the disposable reaction vessel disposed atthe one of the blood coagulation time detectors to start thedouble-reagent blood coagulation reaction.
 4. The automatic analyzeraccording to claim 1, wherein the controller is further configured tocontrol, at a timing at which the one of the samples is to be dispensedby the sample dispensing mechanism, the reaction disk is controlled torotate without the one of the samples being dispensed to one of thereaction cells to thereby produce an empty reaction cell, and the firstreagent dispensing mechanism is then controlled to dispense the one ofthe reagents to the empty reaction cell.
 5. The automatic analyzeraccording to claim 4, wherein the controller is further configured tocontrol the reaction disk to heat the one of the reagents dispensed tothe one of the reaction cells before being suctioned by the secondreagent dispensing mechanism.
 6. The automatic analyzer according toclaim 3, further comprising: a third reagent dispensing mechanismdisposed adjacent to the reaction disk, wherein the controller isfurther configured to control the third reagent dispensing mechanism todispense water or a cleaning agent into the one of the reaction cellsfrom which the one of the reagents was suctioned by the second reagentdispensing mechanism.
 7. The automatic analyzer according to claim 6,wherein the first reagent dispensing mechanism and the third reagentdispensing mechanism are arranged in the biochemical analysis section,and wherein the second reagent dispensing mechanism is arranged in thecoagulation analysis section.
 8. The automatic analyzer according toclaim 1, further comprising: a reagent disk disposed adjacent thereaction disk and on which the one or more reagents are mounted, andwherein the controller is further configured to control the firstreagent dispensing mechanism to suction the one or more reagents fromthe reagent disk and dispense the one or more reagents to the reactiondisk.
 9. The automatic analyzer according to claim 1, furthercomprising: a reaction vessel supply unit disposed adjacent to thedispensing position and that stores a plurality of the disposablereaction vessels; wherein the controller is further configured tocontrol the reaction vessel transfer mechanism to move one of thedisposable reaction vessels from the reaction vessel supply unit to thedispensing position, to move the one of the disposable reaction vesselsfrom the dispensing position to the one of the blood coagulation timedetectors, and to discard the one of the disposable reaction vesselsfrom the one of the blood coagulation time detectors.
 10. The automaticanalyzer according to claim 1, wherein the controller is furtherconfigured to control, at a timing at which the one of the samples isdispensed to the disposable reaction vessel at the dispensing position,the reaction disk is controlled to rotate without one of the samplesbeing dispensed to one of the reaction cells to thereby produce an emptyreaction cell, and the first reagent dispensing mechanism is thencontrolled to dispense the one of the reagents to the empty reactioncell as a reagent for starting the double-reagent blood coagulationreaction.
 11. The automatic analyzer according to claim 10, wherein thecontroller is further configured to control, in accordance with theanalysis item, a period of time where the reagent for starting the bloodcoagulation reaction is heated on the reaction disk before the reagentfor starting the blood coagulation reaction is suctioned by the secondreagent dispensing mechanism.
 12. An automatic analyzer comprising abiochemical analysis section and a blood coagulation time measuringsection, wherein the biochemical analysis section includes: a rotatablereaction disk having a plurality of reaction cells disposed at acircumference thereof; a sample dispensing mechanism that dispenses oneor more samples and is disposed adjacent to the reaction disk andadjacent to a disposable reaction vessel located at a dispensingposition outside of the reaction disk; wherein the sample dispensingmechanism is shared between the biochemical analysis section and theblood coagulation time measuring section; a first reagent dispensingmechanism that dispenses one or more reagents disposed adjacent to thereaction disk; a light source disposed to irradiate a reaction solutionincluding one of the samples and one of the reagents in one of thereaction cells of the reaction disk with light; a photometer disposed todetect transmitted light or scattered light from the irradiated reactionsolution in the one of the reaction cells; a reaction cell cleaningmechanism to clean the reaction solution from the one of the reactioncells; wherein the blood coagulation time measuring section includes: adetector for measuring blood coagulation time; a temperature regulatingblock which has one or more blood coagulation time detectors disposedadjacent to the dispensing position; a reaction vessel transfermechanism to move the disposable reaction vessel from the dispensingposition to one of the blood coagulation time detectors; a secondreagent dispensing mechanism with a reagent heating function disposedadjacent to the reaction disk; and the automatic analyzer furthercomprising a controller that is connected to the rotatable reactiondisk, the sample dispensing mechanism, the first reagent dispensingmechanism, the light source, the photometer, the reaction cell cleaningmechanism, and the blood coagulation time measuring section, wherein thecontroller is configured to control the reaction disk to rotate, thesample dispensing mechanism to dispense one or more of the samples tothe reaction cells located on the reaction disk and dispense one of thesamples to the disposable reaction vessel located at the dispensingposition, and the first reagent dispensing mechanism to dispense one ormore reagents to the reaction cells, wherein the controller is furtherconfigured to control the reaction disk to rotate the light source toirradiate the reaction solution in the one of the reaction cells withlight, and the photometer to detect the transmitted light or thescattered light from the irradiated reaction solution in the one of thereaction cells, and the reaction cell cleaning mechanism to clean thereaction solution from the one of the reaction cells after detection bythe photometer, wherein the controller is further configured to controlthe reaction vessel transfer mechanism to move the disposable reactionvessel from the dispensing position to one of the blood coagulation timedetectors after the sample dispensing mechanism has dispensed the one ofthe samples to the disposable reaction vessel located at the dispensingposition, the one of the blood coagulation time detectors to heat theone of the samples in the disposable reaction vessel, the second reagentdispensing mechanism to suction one of the reagents from one of thereaction cells, the one of the reagents being a coagulation reagent formeasuring blood coagulation time, heat the suctioned coagulationreagent, and dispense the heated coagulation reagent to the disposablereaction vessel disposed at the one of the blood coagulation timedetectors to start a blood coagulation reaction of the one of thesamples and the coagulation reagent in the disposable reaction vesseldisposed at the one of the blood coagulation time detectors, whereinwhen an analysis item measured by the blood coagulation time measuringsection is an analysis item of a single-reagent system the controller isconfigured to control the sample dispensing mechanism such that a sampleis dispensed into a disposable reaction vessel arranged at thedispensing position, and when the sample is an analysis item of a doublereagent system, the sample dispensing mechanism is controlled so as todispense a sample into a reaction cell held in the reaction disk,wherein one cycle time of an analysis operation cycle of the bloodcoagulation time measuring section is a multiple of n (n being a naturalnumber) of a one cycle time of an analysis operation cycle of thebiochemical analysis section, wherein when there is an analysis requestof a biochemical item and a blood coagulation time analysis item and theblood coagulation time analysis item is associated with a single-reagentsystem, the controller determines the order of use of the reaction cellsis determined such that (n−1) number of reaction cells are used forbiochemical analysis among n reaction cells corresponding to one cycletime of the analysis operation of the blood coagulation time measuringsection, and wherein when there is an analysis request of a biochemicalitem and a blood coagulation time analysis item and the bloodcoagulation time analysis item is associated with a double-reagentsystem the controller determines the order of use of the reaction cellssuch that (n−1) number of reaction cells are used for biochemicalanalysis, among n reaction cells corresponding to one cycle time of ananalysis operation cycle for each of the single-reagent and/ordouble-reagent for measuring blood coagulation time, wherein the one ormore blood coagulation time detectors are connected to an amplifier thatamplifies signals from the blood coagulation time detectors and anamplifier controller that controls the amplifier, and wherein thecontroller is further configured to control, on a basis of measurementsfrom the photodetector, the amplifier controller to offset a zero levelof the amplifier before the one of the coagulation time detectorsdetects light during the blood coagulation reaction.
 13. The automaticanalyzer according to claim 12, wherein the zero level of the amplifieris offset for measuring another analysis item different from theanalysis item on which the measurements from the photodetector wereobtained where the sample for the another analysis item and the lateranalysis item are the same.
 14. The automatic analyzer according toclaim 13, wherein a reaction end criterion is based on a peak time of aresult of differentiation of a reaction process data curve obtained fromthe one of the blood coagulation time detectors.